Safety and Efficacy of AEB071 in Metastatic Uveal Melanoma Patients

Uveal Melanoma Clinical Trial

Official title:

A Phase 1 Study of AEB071, an Oral Protein Kinase C Inhibitor, in Patients With Metastatic Uveal Melanoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01430416
• Other study ID #: COEB071X2102
• Secondary ID: 2011-002535-25
• Status: Completed
• Phase: Phase 1
• Start date: December 20, 2011
• Est. completion date: May 22, 2019

Study information

• Verified date: May 2020
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study has two parts, dose escalation and dose expansion. For dose escalation, the primary objective is to estimate the maximum tolerated dose (MTD) of AEB071 in patients with uveal melanoma. For dose expansion, the primary objective is to characterize the safety and tolerability of the MTD of AEB071 in patients with uveal melanoma.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 153
• Est. completion date: May 22, 2019
• Est. primary completion date: May 22, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Uveal melanoma with biopsy proven metastatic disease

• Males and females = 18 years of age

• Consent to biopsy of tumor

• Measurable disease according to RECIST version 1.1

• WHO performance status of = 1

Exclusion Criteria:

• Patients with abnormal laboratory values as defined by the protocol

• Patients who are receiving treatment with strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued prior to study entry

• Patients with impaired cardiac function or clinically significant cardiac diseases as defined by the protocol

• Patients with another malignancy that was treated within the last three years with the exceptions of localized basal cell carcinoma and cervical carcinoma

• Patients with impairment of gastrointestinal function or disease

• Patients with severe systemic infections

• Patients who are known to be HIV positive and/or have active hepatitis B or C infection

• Time since last therapy for treatment of underlying malignancy:

• Cytotoxic chemotherapy: = duration of the most recent cycle of the previous regimen (a minimum of 2 weeks for all)

• Nitrosurea: = 6 weeks

• Biologic therapy: = 4 weeks

• = 5 x PK half-life of a small molecule therapeutic not otherwise defined above

• Patients having undergone major surgery less than 4 weeks prior to enrollment or have not fully recovered from prior surgery

• Women of child-bearing potential unless they are using highly effective methods of contraception during the dosing and for at least 36 hours after last dose. Highly effective contraception as defined in the protocol.

• Patients with primary central nervous system tumors or brain metastases.

• Pregnant or nursing (lactating) women.

Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Melanoma
• Uveal Melanoma
• Uveal Neoplasms

Intervention

Drug:
• AEB071

Locations

Country	Name	City	State
France	Novartis Investigative Site	Paris
Netherlands	Novartis Investigative Site	Leiden
United Kingdom	Novartis Investigative Site	London
United States	Dana Farber Cancer Institute DFCI - Brookline	Boston	Massachusetts
United States	Memorial Sloan Kettering MSKCC 4	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  France,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of dose limiting toxicity during cycle 1 (28 days) - Dose Escalation		cycle 1 (28 days)
Primary	Number of participants reporting serious adverse events and adverse events - Dose Expansion		Baseline, every 28 days
Secondary	Overall response rate (Complete Response (CR) + Partial Response(PR)) to AEB071 using RECIST version 1.1		Baseline, 12 months
Secondary	Progression free survival and time to progression using RECIST version 1.1		Baseline, 12 months
Secondary	Number of patients reporting serious adverse events and adverse events		Baseline, 12 months
Secondary	AEB071/AEE800 pharmacokinetic parameters including Cmax, tmax, AUCt, Ctrough, CL/F, and RA		First 7 months of treatment period
Secondary	Ga genotype in tumor specimens		Baseline, 28 days

External Links

•   Results for COEB071X2102 can be found on the Novartis Clinical Trial Results Website